LRP6 Bidirectionally Regulates Insulin Sensitivity through Insulin Receptor and S6K Signaling in Rats with CG-IUGR

Objective Intrauterine growth restriction followed by postnatal catch-up growth(CG-IUGR)increases the risk of insulin resistance-related diseases.Low-density lipoprotein receptor-related protein 6(LRP6)plays a substantial role in glucose metabolism.However,whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear.This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR.Methods The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction.The mRNA and protein expression of the components in the insulin pathway,LRP6/β-catenin and mammalian target of rapamycin(mTOR)/S6 kinase(S6K)signaling,was determined.Liver tissues were immunostained for the expression of LRP6 andβ-catenin.LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling.Results Compared with the control rats,CG-IUGR rats showed higher homeostasis model assessment for insulin resistance(HOMA-IR)index and fasting insulin level,decreased insulin signaling,reduced mTOR/S6K/insulin receptor substrate-1(IRS-1)serine307 activity,and decreased LRP6/β-catenin in the liver tissue.The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age(AGA)rats led to reductions in insulin receptor(IR)signaling and mTOR/S6K/IRS-1 serine307 activity.In contrast,LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity.Conclusion LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways,IR and mTOR-S6K signaling.LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.

Undifferentiated liver embryonal sarcoma in adults: A report of four cases and literature review

AIM: To evaluate the undifferentiated embryonal sarcoma of liver (UESL) in adults in order to improve its diagnosis and treatment. METHODS: Four primary and one recurrent cases of UESL were clinicopathologically evaluated and immunohistochemically investigated with a panel of antibodies using the EnVision+ system. Relevant literature about UESL in adults was reviewed. RESULTS: Three males and one female were enrolled in this study. Their chief complaints were abdominal pain, weight loss, or fever. Laboratory tests, imaging and pathological features of UESL in adults were similar to those in children. Immunohistochemistry showed evidence of widely divergent differentiation into mesenchymal and epithelial phenotypes. The survival time of patients who underwent complete tumor resection followed by adjuvant transcatheter arterial chemoembolization (TACE) was significantly longer than that of those who underwent surgical treatment alone.CONCLUSION: UESL in adults may undergo pluripotential differentiation and its diagnosis should be made based on its morphological and immunohistochemical features. Complete tumor resection after adjuvant TACE may improve the survival time of such patients.

Microstructure evolution and thixoforming behavior of 7075 aluminum alloy in the semi-solid state prepared by RAP method

The effects of isothermal treatments on the microstructural evolution and coarsening rate of semi-solid 7075 aluminum alloy produced via the recrystallization and partial remelting(RAP) process were investigated. Samples of 7075 aluminum alloy were subjected to cold extrusion, and semi-solid treatment was carried out for 5–30 min at temperatures ranging from 580 to 605°C. A backward-extrusion experiment was conducted to investigate liquid segregation during the thixoforming process. The results revealed that obvious grain coarsening and spheroidization occurred during prolonged isothermal treatments. In addition, higher soaking temperatures promoted the spheroidization and coarsening process because of the increased liquid fraction and the melting of second phases. Segregation of the liquid phase caused by the difference in fluidity between the liquid and the solid phases was observed in different regions of the thixoformed specimens.

Novel CDH1 germline mutations identified in Chinese gastric cancer patients

AIM:To give a comprehensive report of E-cadheringene (CDH1) variations in a population at a high risk for gastric cancer (GC).METHODS:The samples consisted of 178 men and 58 women with a mean age of 62.3 ± 9.4 years and an age range of 30-84 years.A total of 240 cancerfree controls were recruited (mean age of 61.8 ± 10.1 years,age range of 26-82 years).Samples were screened for CDH1 germline mutations by high-resolution melting analysis or directly sequencing.Luciferase reporter assay,RNA splicing assay and bioinformatic analysis were used to evaluate the effect of mutations.RESULTS:Four novel CDH1 sequence alterations were identified in GC patients including a G>T transition 49 bp before the start codon;a three-nucleotide deletion,c.44_46del TGC;one missense mutation,c.604G>A (V202I);and one variation in the intron,c.1320+7A>G.In addition,polymorphism frequencies were observed for CDH1-164delT,-161C>A,-73A>C,c.48+6C>T,c.48+62_48+63delinsCGTGCCCCAGCCC,c.894C>T (A298A),c.1224G>A (A408A),c.1888C>G (L630V),c.2076T>C (A692A),and c.2253C>T (N751N) which is similar to the data reported in http://www.ncbi.nlm.nih.gov/projects/SNP/.RNA splicing analysis suggested that the c.1320+7A>G and c.1224G>A variations did not affect exon splicing ability.Luciferase reporter assay demonstrated that the c.-49T variation might be helpful for E-cadherin transcription,though the increase in transcription activity is limited (only 33%).SIFT score and PolyPhen analysis both demonstrated that the L630V missense mutation probably damages protein function,while the V202I variant does not.CONCLUSION:This study reveals novel mutations in sporadic GC patients which had been poorly investigated for susceptibility genes.

Maternal and Fetal Exposure to Four Carcinogenic Environmental Metals

Objective To examine maternal and fetal exposure levels to four carcinogenic metals,arsenic (As),cadmium (Cd),nickel (Ni),and beryllium (Be),and to investigate their environmental influences.Methods Metal concentrations in maternal and umbilical cord blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS).Environmental factors that might play a role in exposure were analyzed using Mann-Whitney nonparametric U-tests and multiple linear regression.Results The concentrations of As,Cd,and Ni in umbilical cord blood (5.41,0.87,and 139.54 μg/L) were significantly lower than those in maternal blood (6.91,1.93,and 165.93 μg/L).There were significant positive correlations between the maternal and cord concentrations of each carcinogen.Our results showed that:(i) exposures to potentially harmful occupational factors during pregnancy were associated with high levels of maternal As,Cd,and Ni;(ii) living close to major transportation routes (<500 m) or exposure to second-hand smoke during pregnancy increased the maternal Cd levels and (iii) living close to industrial chimneys induced high maternal Ni levels.Multiple linear regression analysis showed that these environmental factors remained significant in models of the influences of these four carcinogens.Conclusion Both mothers and fetuses had been exposed to As,Cd,Ni,and Be.The increased levels of these carcinogens in pregnant women were associated with some detrimental environmental factors,such as occupational exposure,contact with second-hand smoke and living close to major transportation routes or industrial chimneys.

Experimental study on the oxidation behavior and microstructural evolution of NG-CT-10 and NG-CT-20 nuclear graphite

NG-CT-10 and NG-CT-20 are newly developed grades of nuclear-grade graphite from China.In this study,their oxidation behaviors were experimentally investigated using thermal gravimetric analysis.Microstructural evolution before and after oxidation was investigated using scanning electron microscope,mercury intrusion,and Raman spectroscopy.The apparent activation energy of NG-CT-10 nuclear graphite is 161.4 kJ/mol in a reaction temperature range of 550–700℃and that of NG-CT-20 is 153.5 kJ/mol in a temperature range of 550–650℃.The activation energy in the inner diffusion control regime is approximately half that in the kinetics control regime.At high temperatures,the binder phase is preferentially oxidized over the filler particles and small pores are generated in the binder.No new large or deep pores are generated on the graphite surfaces.Oxygen can diffuse along the boundaries of filler particles and through the binder phase,but cannot diffuse into the spaces between the nanocrystallites in the filler particles.Filler particles are oxidized starting at their outer surfaces,and the sizes of nanocrystallites do not decrease following oxidation.

Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal

Acetylcholine(ACh)is an important neuromod-ulator in various cognitive functions.However,it is unclear how ACh influences neural circuit dynamics by altering cellular properties.Here,we investigated how ACh influ-ences reverberatory activity in cultured neuronal networks.We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses,but to a much lesser extent at high doses.Moreover,high doses of ACh caused a longer duration of evoked reverberation,and a higher occur-rence of spontaneous activity.With whole-cell recording from single neurons,we found that ACh inhibited excita-tory postsynaptic currents(EPSCs)while elevating neu-ronal firing in a dose-dependent manner.Furthermore,all ACh-induced cellular and network changes were blocked by muscarinic,but not nicotinic receptor antagonists.With computational modeling,we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations.Thus,ACh modulates network dynamics in a biphasic fashion,probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

CRISPR/Cas9-based mutation reveals Argonaute 1 is essential for pigmentation in Ostrinia fumacalis

Ostrinia fumacalis (Lepidoptera: Pyralidae) is one of the most destructive agricultural pests in Asia. Traditional pest-management methods include sex pheromone capture, transgenic crops that produce Bacillus thuringiensis toxin, and pesticides. Although these strategies control pest populations effectively, they also cause negative side effects, including dramatically increased pesticide resistance, severe pollution, and hazards for human health. Recently developed genome editing tools provide new prospects for pest management and have been successfully used in several species. However, few examples have been reported in the agricultural pest O. fumacalis due to a lack in genomic information. In this report, we identified only one transcript of O. fumacalis Argonaute 1 (OfAgo 1) gene from the genome and cloned the open reading frame. OfAgol presented the maximum expression at the embryo stage or in the fat body during the larval stages. To understand its function, an OfAgol mutant was constructed using the Clustered Regularly Interspaced Short Palindromic Repeat/RNA-guided Cas9 nuclease (CRISPR/Cas9). Mutagenesis of OfAgol disrupted cuticle pigmentation by dowregulating micro RNAs and pigmentation-related genes. This is the first report for the cloning and functional analysis of OfAgol, revealing a role of OfAgol in cuticle pigmentation. The current report also established a CRISPR/Cas9 system in O. fumacalisy providing a new insight for pest management.

Wide Operational Range Processor Power Delivery Design for Both Super-Threshold Voltage and Near-Threshold Voltage Computing

因为许多先进功率管理技术被采用，现代处理器的负担功率范围极大地被扩大频率可伸缩，增加的涡轮，和近阀值的电压(NTV ) ，例如动态电压技术。然而，因为力量交货的效率与不同负担条件极大地变化，常规力量交货图案不能在全部电压光谱上维持高效率，并且节省的获得的力量可以是由在力量交货的力量损失的偏移量。我们建议 SuperRange，一个宽运作的范围力量交货单位。SuperRange 补充在薄片上电压管理者和离开薄片电压管理者的功率交货能力。在 SuperRange 上，我们分析它的力量变换特征并且建议一个电压管理者(VR ) 知道的力量管理算法。而且因为越来越多的核心在一个 singe 薄片上是综合的，多重 SuperRange 单位能服务同样基本的积木造，以一个高度可伸缩的方法，有更大的力量能力的更强大的力量交货分系统。试验性的结果表演 SuperRange 单位提议 1x 和 1.3x 更高比另外的二常规力量交货在 NTV 区域策划并且展出一般水准的驱动变换效率(PCE ) 在全部运作的范围上的 70% PCE。它也展出优异跳回到抑制力量的系统。

Metallurgy of aluminum-inspired formation of aluminosilicate-coated nanosilicon for lithium-ion battery anode

Modification of Si anode with various coating matrixes is a promising strategy to resolve the unsta-ble solid electrolyte interphase issues.However,the com-plex preparation process and inherently weak interaction between Si and other matrixes impede its practical appli-cation.Inspired by the metallurgical process of aluminum,an aluminosilicate matrix was prepared as coating layer on the surface of Si nanoparticles after heat treatment.Si nanoparticles with a uniform native oxide layer were used as seed crystals for the adsorption of aluminum hydroxide.The strong symbiosis and bond between alumina and silica,such as mullite(3Al_(2)O_(3)·2SiO_(2))or kaolin(Al2O_(3)·SiO_(2)·2H_(2)O),provide homogeneous and durable contact coating layer.The as-produced Si/SiO_(2)·Al_(2)O_(3)composite delivers a charge capacity of 1440 mAh·g^(-1)at 100 mA·g^(-1)and remains 879 mAh·g^(-1)at 3 A·g^(-1).After 200 cycles,the capacity retention remains high at 76%.The enhanced properties were ascribed to SiO_(2)·Al_(2)O_(3)syner-gistic composite coating layer,which could hinder the interfacial side chemical reaction and buffer volume change of Si.

Intracoronary pressure gradient measurement in acute myocardial infarction patients with the no-reflow phenomenon during primary percutaneous coronary intervention

Background:Various experimental and clinical studies have reported on coronary microcirculatory dysfunction("no-reflow"phenomenon).Nevertheless,pathogenesis and effective treatment are yet to be fully elucidated.This study aimed to measure the intracoronary pressure gradient in the no-reflow artery during emergent percutaneous coronary intervention and explore the potential mechanism of no-reflow.Methods:From September 1st,2018 to June 30th,2019,intracoronary pressure in acute myocardial infarction patient was continuously measured by aspiration catheter from distal to proximal segment in the Department of Coronary Care Unit,Tianjin Chest Hospital,respectively in no-reflow arteries(no-reflow group)and arteries with thrombolysis in myocardial infarction-3 flow(control group).At least 12 cardiac cycles were consecutively recorded when the catheter was pulled back.The forward systolic pressure gradient was calculated as proximal systolic pressure minus distal systolic pressure.Comparison between groups was made using the Student t test,Mann-Whitney U-test or Chi-square test,as appropriate.Results:Intracoronary pressure in 33 no-reflow group and 26 in control group were measured.The intracoronary forward systolic pressure gradient was-1.3(-4.8,0.7)and 3.8(0.8,8.8)mmHg in no-reflow group and control group(Z=-3.989,P<0.001),respectively,while the forward diastolic pressure gradient was-1.0(-3.2,0)and 4.6(0,16.5)mmHg in respective groups(Z=-3.851,P<0.001).Moreover,the intracoronary forward pressure gradient showed significant difference between that before and after nicorandil medication(Z=-3.668,P<0.001 in systolic pressure gradient and Z=-3.530,P<0.001 in diastolic pressure gradient).Conclusions:No reflow during emergent coronary revascularization is significantly associated with local hemodynamic abnormalities in the coronary arteries.Intracoronary nicorandil administration at the distal segment of a coronary artery with an aspiration catheter could improve the microcirculatory dysfunction and resume normal coronary pressure gradient.Clinical trial registration:www.ClinicalTrials.gov(No.NCT 03600259).

一种新型隐身无人艇气水混合层水动力作用研究

该文研究的隐身型无人艇艏部为双体内凹结构,靠近艉部逐渐转换为多体,中间附体厚度沿纵向逐渐变大。为了研究此无人艇在不同航速下的阻力性能,首先采用物理水池试验研究了初始倾角、有无艏部整流板和排水量对艇体阻力性能的影响规律,然后基于CFD技术探讨了无人艇内凹滑行腔内气水层对艇体阻力性能影响的内在机制。计算结果表明:低速排水阶段内凹滑行腔聚集的兴波会造成阻力的增加,出现低速阻力峰;随着速度的增加,无人艇进入滑行阶段,内凹滑行腔产生气水混合层,当体积弗劳德数为4.69时,出现高速阻力峰,在艏部整流板的引导下,更多气体的进入使腔体的气水混合层加厚,将艇体托起,跨过阻力峰。研究表明双体内凹型腔和艏部整流板有助于兴波的聚集和气水混合层的形成。随着气水混合层对艇体支撑作用的提升,多体滑行艇高速滑行时的阻力处于下降趋势。上述结论可为隐身多体无人艇的设计及优化提供技术支撑。

TSV Minimization for Circuit Partitioned 3D SoC Test Wrapper Design

Semiconductor technology continues advancing,while global on-chip interconnects do not scale with the same pace as transistors,which has become the major bottleneck for performance and integration of future giga-scale ICs.Threedimensional(3D) integration has been proposed to sustain Moore's law by incorporating through-silicon vias(TSVs) to integrate different circuit modules in the vertical direction,which is believed to be one of the most promising techniques to tackle the interconnect scaling problem.Due to its unique characteristics,there are many research opportunities,and in this paper we focus on the test wrapper optimization for the individual circuit-partitioned embedded cores within 3D System-onChips(SoCs).Firstly,we use existing 2D SoCs algorithms to minimize test time for individual embedded cores.In addition,vertical interconnects,i.e.,TSVs that are used to construct the test wrapper should be taken into consideration as well.This is because TSVs typically employ bonding pads to tackle the misalignment problem,and they will occupy significant planar chip area,which may result in routing congestion.In this paper,we propose a series of heuristic algorithms to reduce the number of TSVs used in test wrapper chain construction without affecting test time negatively.It is composed of two steps,i.e.,scan chain allocation and functional input/output insertion,both of which can reduce TSV count significantly.Through extensive experimental evaluations,it is shown that the test wrapper chain structure designed by our method can reduce the number of test TSVs dramatically,i.e.,as much as 60.5% reductions in comparison with the random method and 26% in comparison with the intuitive method.

Role of digestive protease enzymes and related genes in host plant adaptation of a polyphagous pest,Spodoptera frugiperda

The evolutionary success of phytophagous insects depends on their ability toefficiently exploit plants as a source of energy for survival.Herbivorous insects largelydepend on the efficiency,flexibility,and diversity of their digestive physiology and sophistication of their detoxification system to use chemically diverse host plants as foodsources.The fall armyworm,Spodoptera frugiperda(J.E.Smith),is a polyphagous pest ofmany commercially important crops.To elucidate the ability of this insect pest to adaptto host plant mechanisms,we evaluated the impact of primary(corn)and alternate(rice)host plants after 1l generations on gut digestive enzymatic activity and expression profiles of related genes.Results indicated that the total protease and classspecific trypsinand chymotrypsinlike protease activity of S.frugiperda significantly differed among hostplant treatments.The classspecifiq protease profiles greatly differed in S.frugiperdamidguts upon larval exposure to different treatments with inhibitors compared with treatments without inhibitors.Similarly,the single and cumulative effects of the enzymespecific inhibitors TLCK,TPCK,and E64 significantly increased larval mortality and reduced larval growth/mass across different plant treatments.Furthermore,the quantitativereverse transcription polymerase chain reaction results revealed increased transcription oftwo trypsin(SfTry3,SfTry7)and one chymotrypsin gene(Sfchym9),which indicatedthat they have roles in host plant adaptation.Knockdown of these genes resulted in significantly reduced mRNA expression levels of the trypsin genes.This was related to theincreased mortality observed in treatments compared with the dsRED control.This resultindicates possible roles of S.frugiperda gut digestive enzymes and related genes in hostplant adaptation.

Evaluating and Constraining Hardware Assertions with Absent Scenarios

Mining from simulation data of the golden model in hardware design verification is an effective solution to assertion generation.While the simulation data is inherently incomplete,it is necessary to evaluate the truth values of the mined assertions.This paper presents an approach to evaluating and constraining hardware assertions with absent scenarios.A Belief-fail Rate metric is proposed to predict the truth/falseness of generated assertions.By considering both the occurrences of free variable assignments and the conflicts of absent scenarios,we use the metric to sort true assertions in higher ranking and false assertions in lower ranking.Our Belief-failRate guided assertion constraining method leverages the quality of generated assertions.The experimental results show that the Belief-failRate framework performs better than the existing methods.In addition,the assertion evaluating and constraining procedure can find more assertions that cover new design functionality in comparison with the previous methods.